Macular edema is swelling within the retina within the critically important central visual zone at the posterior pole of the eye. An accumulation of fluid within the retina tends to distract the neural elements from one another and from their local blood supply, creating a dormancy of visual function in the area. Usually the process is self-limiting, but permanent visual disability occasionally results. Often times, the swelling may take many months to clear. The precise mechanism by which swelling is triggered is uncertain, but it is probable that certain natural metabolic toxins may play an important role in the disease process. Swelling may also follow the implantation of plastic lenses after cataract surgery, particularly if there is a breech in the lens capsule which segregates the vitreous gel from the fluid filled anterior chamber. Long standing macular edema after cataract surgery is one of the most frustrating situations in all of opthamology, and is remarkably common.
It was first reported by Cox et al, Arch. Ophthalmol., Vol. 106, Sept. 1988, pp. 1190-95, that oral acetazolamide (DIAMOX.RTM.) can cause resolution of chronic macular edema of various causes. In this study, 16 of 41 patients showed a reproducible response to the drug with partial or complete resolution of edema and improvement of visual acuity. The therapeutic effect occurred in more than half of the patients with inherited outer retinal disease or uveitis, but in none with primary retinal vascular disorders. Additional studies have corroborated Cox's findings with acetazolamide (Fishman et al., Arch. Ophthalmol. 1989; 107:1445-1452 and Chen et al., Invest. Ophthalmol. Vis. Sci. 1991; 31:1914-1918) and others have utilized the carbonic anhydrase inhibitor methazolamide (Fishman et al., Arch. Ophthalmol. 1993; 111:1640-1646).
Studies of patients who have proven to be responsive to acetazolamide treatment typically show pigment epithelial cell dysfunction. These cells, which line the innermost layer of the choroid, have villi-like projections which interdigitate with the retinal photoreceptors. This flexible but intimate association between pigment epithelial cells and photoreceptors is of critical importance to retinal health. The photoreceptors are highly active metabolically and produce waste products at a great rate. The pigment epithelial villi typically absorb catabolites, regenerate photo pigment and provide nutrients via their closely associated choriocapillaris vascular network. Fluorescein angiography of the pigment epithelium in individuals with macular edema who have shown to be responsive to acetazolamide demonstrate leakage of dye into the photoreceptor area. This leakage is inhibited by treatment with acetazolamide.
There are a number of theories as to how carbonic anhydrase inhibitors (CAIs) might work on macular edema however none have been conclusively detemined. At least 14 different etiologic subtypes of macular edema exist, and it is probable that some will prove to be more responsive to topical CAI treatment than other types. Some of the abovementioned studies lay a basis for this.
Another even more common chronic condition which has typically been presumed to be irreversible is macular degeneration. Macular degeneration is the most common cause of acquired legal blindness. Instead of fluid accumulating in the outer retina, hard accumulations of lipofuscin, a metabolic waste product, tend to accumulate between the photoreceptors and the villi of the retina pigment epithelium. These accumulations gradually enlarge, and in their early pathologic phase create discrete accumulations known as drusen. The lipofuscin is belived to accumulate as a result of a process known as apoptosis, a breaking off of the photoreceptor elements. Shedding of the cellular components of the photoreceptors is constantly occurring in a healthy retina. Good retinal pigment epithelial metabolism generally insures a rapid clearance of such catabolic byproducts of vision. It is interesting to consider that an improved local circulation or a stabilization of membrane pH gradience might retard or prevent the accumulation of lipofuscin. As drusen accumulate in number and begin to coalesce, vast areas of retinal photoreceptors become permanently disengaged from their neighboring retinal pigment epithelial villi. The sections of retina so effected become blind. The greatest propensity among the aging population is for drusen to accumulate in the very central area of vision, the macula. Current therapy lacks any substantive clinical scientific basis with zinc in tablet form as one attempted method of treatment. Thus, a method of treating and/or preventing age-related macular degeneration would be welcomed by the medical community.